Transcriptional enhancers are known as fundamental non-coding elements in our genomes that control the spatial and temporal expression patterns of genes. Along the linear chromosome enhancers can be located hundreds of thousands of base-pairs away from their target gene(s) and recent epigenomic profiling studies predict more than a million of such enhancers to be present in human genomes.
In our lab we use a combination of molecular genetics, functional genomics and genome engineering to define fundamental gene regulatory mechanisms that control mammalian heart formation and/or cardiac reprogramming. This knowledge has direct relevance for our understanding of congenital heart disease and carries therapeutic potential for heart muscle repair.
Currently, our main areas of interest are:
1) Cardiac enhancer function in heart development and disease.
We are using CRISPR/Cas9 genome editing, transgenic fluorescent reporter tagging and single-cell profiling in mouse embryos to functionally dissect the cardiac enhancer landscapes of transcription factor (TF) genes that are essential for heart formation. Identification of cardiac enhancers and understanding of their cellular specificities and regulatory relationships will be important to establish accurate mechanistic links between gene networks, cardiac development and disease-associated non-coding genomic mutations.
2) Cis-regulatory mechanisms underlying cardiac reprogramming.
We are planning to implement a CRISPR-based approach for concerted activation of developmental TFs to enable cardiac trans-differentiation in target cell types. It is our goal to use this system to uncover genomic cis-regulatory modules in control of the cardiac reprogramming process which holds therapeutic potential for regeneration of infarcted cardiac tissue and heart muscle repair.